Hallazgos clínicos y epidemiológicos en la neurofibromatosis tipo 1 y el complejo esclerosis tuberosa en una serie de pacientes pediátricos / Clinical and epidemiological findings in neurofibromatosis type 1 and tuberous sclerosis complex in a series of pediatric patients

Resumen: Introducción: La neurofibromatosis tipo 1 (NF1) es una entidad genética con una incidencia de 1 entre 2,500 a 3,500 nacimientos. Por su parte, el complejo esclerosis tuberosa (CET) presenta una incidencia de 1 entre 6,000 a 10,000 nacimientos. Ambas entidades neurocutáneas cursan con un patrón de herencia autosómico dominante, expresividad variable y la morbimortalidad se encuentra asociada a complicaciones multisistémicas. El objetivo de este trabajo fue exponer las características clínicas y epidemiológicas de una serie de pacientes pediátricos con diagnóstico de NF1 y CET atendidos en la Unidad de Genética Médica de la Universidad de Los Andes. Métodos: Este trabajo corresponde a una serie de casos de pacientes menores de 16 años atendidos en un período de 11 años, que cumplan con los criterios diagnósticos de NF1 y CET según los consensos para cada entidad. Resultados: Se estudiaron 89 pacientes, 73 con NF1 y 16 con CET. Presentaron dos criterios para NF1, 58 (79.45%) pacientes, y las máculas café con leche fueron las más frecuentes y presentes en todos los casos; 10 pacientes (62.50 %) presentaron dos criterios mayores para el CET, y las máculas hipocrómicas estuvieron igualmente presentes en todos los casos. Conclusiones: Este estudio muestra la forma de presentación clínica de las dos entidades neurocutáneas más frecuentes. Se discuten los criterios diagnósticos con el objeto de identificarlos a edades más tempranas y poder brindar una evaluación médica interdisciplinaria, tratamiento y un oportuno asesoramiento genético familiar.

Abstract: Background: Neurofibromatosis type 1 (NF1) is a genetic entity with an incidence of 1 in 2,500 to 3,500 births. Tuberous sclerosis complex (TSC) has an incidence between 1 in 6,000 to 10,000 births. Both neurocutaneous entities present an autosomal dominant inheritance pattern, variable expressivity and their morbidity and mortality is associated with multisystemic complications. The aim of this study was to present the clinical and epidemiological characteristics of a series of pediatric patients diagnosed with NF1 and TSC, who were treated in the Medical Genetics Unit of the Universidad of Los Andes. Methods: This work corresponds to a series of cases of patients under 16 years of age served in a period of 11 years, who met the diagnostic criteria of NF1 and CET according to the consensus for each entity. Results: We studied 89 patients, 73 with NF1 and 16 with TSC. 58 (79.45%) of the patients presented two criteria for NF1, with café-au-lait macules being the most frequent and present in all cases. 10 (62.50%) of the patients presented two major criteria for TSC; hypochromic macules were equally present in all cases. Conclusions: This study shows the clinical presentation of the two most frequent neurocutaneous entities. Diagnostic criteria are discussed in order to perform them at younger ages and to provide an interdisciplinary medical evaluation, treatment and timely family genetic counseling.

Analysis of twenty pediatric cases of tuberous sclerosis complex: Are we doing enough.

Background: Tuberous sclerosis complex (TSC) is a neuro-cutaneous disease characterized by hamartoma formation in various organs particularly the skin, brain, eye, kidney, heart and lungs. Patients usually have multisystem involvement and thus present to different medical specialties with varied complaints while the true nature of the disease and the hidden manifestations may remain unattended. A im: To assess the frequency and characteristics of various cutaneous and systemic manifestations in TSC and the total impact on different system in a cohort of pediatric patients. Methods: The study included 20 patients fulfilling the diagnostic criteria for TSC from dermatology, pediatrics, and neurology department. Detailed history, examination, and investigations such as chest X-ray, electrocardiography (ECG), ultrasonography (USG) abdomen, echocardiography, fundoscopy, computed tomography (CT) scan of brain and abdomen were done. Results: Dermatological manifestations included ash leaf macules, angiofibromas, shagreen patch, and fibrous plaque. Systemic findings observed were subependymal calcified nodules, subependymal giant cell astrocytoma, cortical tubers, renal cysts, angiomyolipomas, lung cyst, retinal hamartomas, mental deficits and epilepsy. Limitation: Wechsler's Intelligence Scale for Children would have been more appropriate for assessing the intelligence. Dental check-up was not done in our group of patients. Conclusion: Our study highlights the wide variety of cutaneous and systemic manifestations of TSC. The study emphasizes the need for comprehensive multidisciplinary treatment and periodic follow-up which are necessary for appropriate management of this multisystem disorder. Counseling regarding education and rehabilitation of the patients and genetic counseling of parents are important.

Tuberous sclerosis with rhabdomyoma.

Tuberous sclerosis is a neurocutaneous syndrome characterized by abnormalities of both the integument and central nervous system. We present a case of tuberous sclerosis with rhabdomyoma in the heart. This was a 1½-year-old female child with infantile spasms and rhabdomyoma in heart with mother having neurocutaneous markers of tuberous sclerosis. Magnetic resonance imaging brain and electroencephalography findings were consistent with diagnosis.

Presentación de caso radiológico: Esclerosis tuberosa / Radiologic case presentation. Tuberous sclerosis

Se presenta un caso de una mujer de 27 años, quien acude al Cuerpo de Guardia con dolor abdominal moderado de reciente comienzo. Al examen físico, se constata una masa abdominal que ocupaba ambos flancos. Luego de los estudios clínicos e imagenológicos, se comprobó la presencia de angiomiolipomas renales bilaterales, nódulos subependimarios y lesiones en piel por lo que se diagnosticó esclerosis tuberosa. La esclerosis tuberosa es una enfermedad neurocutánea caracterizada por cambios hamartomatosos en los pulmones, cerebro, riñones, piel, corazón y otros órganos. Para el diagnóstico se aplican criterios basados en el hallazgo de manifestaciones mayores y menores. En esto, la Imagenología tiene un importante papel(AU)

A 27 year old woman was given to the emergency department with mild, acute onset of right side abdominal pain. Clinical examination revealed firm masses bilaterally occupying almost the entire abdomen. Because the presence of bilateral angiomyolipomas, subependymal tuberous and adenoma sebaceum of the skin the patient was diagnosed as having a case of tuberous sclerosis . TS is a neurocutaneous disease characterized by hamartomatous changes in the lungs, brain, kidneys, skin, heart and others organs. The diagnostic criteria consisted of a set of major and minor diagnostic features. The imagenology plays a very important role(AU)

Rare association of Turner syndrome with neurofibromatosis type 1 and tuberous sclerosis complex.

We report a rare association of Turner syndrome with both Neurofibromatosis type I and Tuberous Sclerosis. The patient had XOkaryotype with Turners stigmata and also had features of Neurofibromatosis 1 in the form of significant café-au-lait spots and Plexiform neurofibroma along with typical features of Tuberous Sclerosis complex. Pedigree analysis revealed that the elder brother of the proband in the family also suffered from Tuberous Sclerosis without the manifestation of Neurofibromatosis or any other genetic disorders. We hypothesize that these associations could be due to new independent mutations and also increased maternal and paternal age in a pre-disposition of Turner syndrome.

Pulmonary tuberous sclerosis

Pulmonary involvement in tuberous sclerosis is very rare and seems to be associated with a more benign course. We present a 21-year-old woman with bilateral angiomyolipoma. She developed spontaneous pneumothorax which was successfully managed by tube thoracostomy. No recurrence of pneumothorax has been observed up to the present [4 years follow-up]

Tuberous sclerosis

Tuberous Sclerosis is an autosomal dominant disorder. It occurs with frequency of 1:5800-30000. It present as cutaneous and systemic manifestations. We report here a case of Tuberous sclerosis in a 10 month old infant who presented with infantile spasms and ash leaf lesions. Treatment with steroids showed good response

Epidemiologia genética e clínica da esclerose tuberosa / Genetic and clinical epidemiology of tuberous sclerosis

O presente trabalho aborda aspectos epidemiológicos e genéticos da Esclerose Tuberosa, uma doença multissistêmica e complexa, caracterizada tradicionalmente por Angiofibromas faciais(anteriormente confundido com Adenoma Sebáceo)Epilepsia e Retardo Mental. A etiopatogenia da doença só recentemente começou a ser elucidada. A ocorrência varia de 1/10.000 a 1/50.000 em todas as populações e grupos étnicos. A proporção sexual é 1,0.A herança é compatível com o medelo autossômico dominante com penetrância incompleta, embora tenha sido estimado que cerca de 85 por cento dos casos resultam de mutações novas. A Esclerose Tuberosa está ligada a pelo menos dois Ioci, o TSC1 no cromossomo 9 (9q34.3) e o TSC2 no cromossomo 16 (16p13.3). O gene TSC2 codifica uma proteína, a tuberina, que funciona como um supressor de tumor. A tríade clássica da Esclerose Tuberosa é confirmada em apenas um terço dos casos, no restante a doença pode apresentar uma ampla variedade de sinais e sintomas, principalmente manifestações cutâneas, hamartomas e tumores de vários órgãos e tecidos